title: Predicting small ligand binding sites in proteins using backbone structure.
abstract: BACKGROUND
  Specific non-covalent binding of metal ions and ligands, such as nucleotides and cofactors, is essential for the function of many proteins. Computational methods are useful for predicting the location of such binding sites when experimental information is lacking. Methods that use structural information, when available, are particularly promising since they can potentially identify non-contiguous binding motifs that cannot be found using only the amino acid sequence. Furthermore, a prediction method that can utilize low-resolution models is advantageous because high-resolution structures are available for only a relatively small fraction of proteins.
  
  
  RESULTS
  SitePredict is a machine learning-based method for predicting binding sites in protein structures for specific metal ions or small molecules. The method uses Random Forest classifiers trained on diverse residue-based site properties including spatial clustering of residue types and evolutionary conservation. SitePredict was tested by cross-validation on a set of known binding sites for six different metal ions and five different small molecules in a non-redundant set of protein-ligand complex structures. The prediction performance was good for all ligands considered, as reflected by AUC values of at least 0.8. Furthermore, a more realistic test on unbound structures showed only a slight decrease in the accuracy. The properties that contribute the most to the prediction accuracy of each ligand were also examined. Finally, examples of predicted binding sites in homology models and uncharacterized proteins are discussed.
  
  
  BACKGROUND
  Binding site prediction results for all PDB protein structures and human protein homology models are available at http://sitepredict.org/.
authors.affiliation: Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA. bordner.andrew@mayo.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bordner
mesh_terms: D001185:Artificial Intelligence; D001665:Binding Sites; D030562:Databases, Protein; D008024:Ligands; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012984:Software; D040681:Structural Homology, Protein
chemical_list: D008024:Ligands; D011506:Proteins